Woman reports decreased vision, diplopia

Bilateral papilledema and ophthalmoplegia were found on examination.

Priti Batta

Namrata Nandakumar

A 20-year-old woman presented to the emergency room with a 3-day history of progressively decreasing vision in both eyes. She also described binocular diplopia in almost all directions of gaze. A review of systems was notable for 3 weeks of pressure-like headaches, neck stiffness and general fatigue. The patient denied any pain with eye movement, nausea, vomiting or ringing in her ears. She denied any previous similar episodes.

Her ocular history was unremarkable. Her medical history was significant for recent pregnancy and uncomplicated delivery 6 months before presentation, as well as obesity, remote opiate addiction and borderline hypertension. She was recently diagnosed with an upper respiratory infection, for which she was being treated with azithromycin. Other outpatient medications at the time of presentation included hydrochlorothiazide, methadone, ibuprofen, cyclobenzaprine and prochlorperazine.

On examination, the patient’s visual acuity without correction was light perception in the right eye and 20/30 in the left eye, with no improvement on pinhole refraction. Her pupils measured 8 mm bilaterally, with sluggish constriction to 6 mm in the right eye and 5 mm in the left eye. She had a relative afferent pupillary defect in the right eye. IOPs were 17 mm Hg and 15 mm Hg, respectively. She had generalized limitation of extraocular motility in both eyes (Figure 1). Her anterior segment examination was normal. Dilated fundus examination was remarkable for bilateral optic nerve head swelling with peripapillary hemorrhages (Figure 2). Humphrey visual fields demonstrated severe constriction in both eyes.

Figure 1. External photographs of eye movements at initial presentation. Note the bilateral abduction and adduction deficits, as well as bilateral vertical gaze deficits. Images: Goren JF, Strominger MB, Hedges TR

Figure 2. Bilateral fundus photographs reveal severe papilledema in both eyes with peripapillary hemorrhages.

The patient underwent MRI of the brain with arteriography and venography, which was unremarkable. The patient also had a lumbar puncture that demonstrated an opening pressure of greater than 50 cm of water. The cell count in tube four demonstrated no white blood cells, 240 red blood cells, protein 23, glucose of 67, no organisms or cells on Gram stain, and a negative cerebrospinal fluid (CSF) culture. The patient had a normal blood pressure throughout her hospital admission.

What is your diagnosis?

Bilateral papilledema and ophthalmoplegia

The differential diagnosis of bilateral papilledema includes idiopathic intracranial hypertension, cerebral venous obstruction, extracranial venous obstruction, dural arteriovenous malformation, meningitis and malignant hypertension.

Differential diagnosis

Idiopathic intracranial hypertension is high on this patient’s differential diagnosis, given her age, obesity and history of recent pregnancy. Cerebral venous obstruction, which can be secondary to trauma, childbirth, hypercoagulability, neoplastic obstruction or middle ear infection, could also cause the symptoms seen in this patient. However, this diagnosis was ruled out with a negative magnetic resonance venography. Likewise, systemic or localized extracranial venous obstruction, for example caused by a radical neck dissection, could cause a similar decrease in venous outflow and consequent increase in intracranial pressure, but again this can be ruled out by history and imaging. Similarly, a dural arteriovenous malformation would also be detected on imaging and would be unlikely in a patient of this age with no history of trauma. Meningitis can be ruled out given the absence of white blood cells or organisms on Gram stain and smear, especially in light of a normal CSF protein and glucose. Malignant hypertension is unlikely because this patient had a normal blood pressure.

Diagnosis

Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, typically presents with signs and symptoms of elevated intracranial pressure, such as headache, nausea and vomiting. Additionally, patients may complain of pulsatile tinnitus, transient visual obscurations secondary to papilledema, visual field loss and diplopia secondary to abducens nerve palsy.

The incidence of IIH peaks in the third decade, and there is a strong female predilection. IIH is associated with obesity, hypervitaminosis A, steroid use or withdrawal, tetracyclines, nalidixic acid, cyclosporine and oral contraceptive use. Hormonal changes such as pregnancy and other hormonal abnormalities have also been associated; however, IIH has not been definitely associated with any particular endocrinologic dysfunction. In addition, the mechanism for the increase in intracranial pressure in IIH remains unclear, although impaired absorption of the CSF across arachnoid granulations into the dural venous sinuses is thought to be a contributing factor.

The diagnostic criteria for IIH includes high-pressure headaches, papilledema, CSF opening pressure of greater than 25 cm of water, normal CSF constituents, normal brain imaging without evidence of venous obstruction, and the absence of additional localizing symptoms other than lateral rectus palsy.

Management

Treatment of IIH depends on the patient’s symptoms and visual function. The disease can be self-limited or lead to severe visual impairment and intractable headaches. For patients who are obese, weight loss is always part of the treatment protocol. Some patients are treated aggressively with low-calorie diets or even with gastric bypass surgery, as improvements in outcome have been demonstrated with as little as 10 pounds of weight loss. Medications that lower intracranial pressure are typically also employed. First-line therapy is usually oral acetazolamide, a carbonic anhydrase inhibitor that decreases CSF production. Furosemide can be used in patients unable to tolerate acetazolamide. If there is severe or progressive visual impairment or if headaches persist despite medical therapy, then a surgical approach may be employed in addition to medical treatment. Options include optic nerve sheath fenestration or a CSF diversion procedure such as a lumbar peritoneal shunt or a ventriculoperitoneal shunt. If visual impairment is the predominant symptom, optic nerve sheath fenestration is generally the favored technique, whereas if headache is the major symptom, shunting procedures are typically utilized. There has not been a randomized controlled clinical trial comparing outcomes of these different surgical procedures to date.

This patient had the classic signs and symptoms of IIH, but also demonstrated near-complete ophthalmoplegia, suggesting partial bilateral third nerve palsies in addition to sixth nerve palsies. Ocular motility disturbances other than abducens nerve palsy are exceedingly rare manifestations of true IIH and often are associated with cerebral venous thrombosis rather than IIH. The cause of sixth nerve palsy in IIH is presumed to be secondary to increased intracranial pressure, causing kinking of the nerve over nearby blood vessels. There are rare case reports documenting ophthalmoparesis associated with IIH, typically in cases of extremely high CSF pressures.

The patient was admitted to the hospital and treated with high-dose systemic acetazolamide. In addition, given the severity of visual dysfunction, she underwent a right optic nerve sheath fenestration. The patient was discharged home on oral acetazolamide and has been followed closely as an outpatient by the neuro-ophthalmology and neurology services. The patient has had a dramatic improvement in visual acuity to nearly 20/20 in both eyes. Her ophthalmoplegia has also resolved. She eventually developed bilateral optic atrophy, and her visual fields remain constricted in both eyes.

References:

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• Jordana F. Goren, MD, Mitchell B. Strominger, MD, and Thomas R. Hedges III, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Priti Batta, MD, and Namrata Nandakumar, MD. Drs. Batta and Nandakumar can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.